Cytoskeletal regulation of the Hippo and Notch1 signaling pathways in endometrial stromal cell decidualization and endometriosis
子宫内膜基质细胞蜕膜化和子宫内膜异位症中 Hippo 和 Notch1 信号通路的细胞骨架调节
基本信息
- 批准号:10385956
- 负责人:
- 金额:$ 3.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAffectAgeBasic ScienceCellsCellular MorphologyCellular biologyCyclic AMPCytoskeletonDecidual Cell ReactionsDefectDevelopmentDiseaseDysmenorrheaEmbryoEndometrialEndometrial Stromal CellEnzymesFailureFemale infertilityFocal Adhesion Kinase 1Functional disorderHumanHuman Chorionic GonadotropinImpairmentInfertilityInterleukin-1 betaKnowledgeLeadLigandsLuteal PhaseMediatingMolecularMolecular BiologyMorphologyMyosin ATPaseMyosin Light Chain KinaseNOTCH1 geneNotch Signaling PathwayPathologyPathway interactionsPelvic PainPhosphorylationPhosphotransferasesPlayPregnancyProcessProgesteroneProteinsRegulationReproductive ProcessResearchRoleSignal PathwaySignal TransductionSignaling MoleculeSiteSmooth Muscle Actin Staining MethodStromal CellsStructureTechnical ExpertiseTestingTissuesVinculinWomancareercell transformationdiagnostic biomarkerendometriosiseutopic endometriumexperienceinsightmembernotch proteinnovelprogramsprotein protein interactionreproductivereproductive successresponseskillssteroid hormonesuccesstrafficking
项目摘要
PROJECT SUMMARY
Endometrial stromal cell decidualization is critical to reproductive success. The decidualization process involves
morphological and functional changes of endometrial stromal cells. The actin-myosin cytoskeleton contributes
to changes in cell morphology and likely plays a role in the intracellular shuttling of proteins critical in
decidualization. Decidualization is the terminal differentiation of human endometrial stromal cells in response to
rising progesterone levels and is maintained throughout pregnancy by embryonic signals and progesterone.
Defects in this process are associated with reproductive failure in diseases such as endometriosis.
Endometriosis is characterized by endometrial-like tissue found at ectopic sites and the disease is associated
with significant pelvic pain, infertility, and dysmenorrhea, but its pathophysiology remains elusive. The aim of this
proposal is to understand the functional role of the cytoskeleton in the decidualization process and determine
how this is aberrant in the stromal cells of women with endometriosis which may contribute to their infertility. The
Hippo target homologs, YAP and TAZ, and Notch1 signaling are known to mediate the initiation of the
decidualization response, but what regulates these pathways during decidualization remains unknown. Previous
research has also shown that significant changes in the cytoskeleton are associated with endometrial stromal
cell decidualization. In addition, cytoskeleton dynamics and Notch1 and YAP/TAZ signaling are dysregulated in
endometriosis. We hypothesize that the cytoskeleton mediates the decidualization response and is defective in
infertile women with endometriosis. To test our overall hypothesis in Aim 1 we will investigate direct actin-myosin
cytoskeleton regulation of the Hippo/YAP/TAZ and NOTCH1 signaling pathways in the context of endometrial
stromal cell decidualization and in Aim 2, we will determine how an altered cytoskeleton compromises
decidualization in stromal cells from infertile women with endometriosis. The proposed studies will address
cytoskeletal regulation of key molecular mechanisms that regulate stromal cell decidualization. These studies
will greatly expand the technical expertise in cell and molecular biology of the applicant. These experiences
combined with professional development supported by the sponsor, co-sponsor, and program will help the
applicant to develop the skill set required to pursue a career in basic science research.
项目摘要
子宫内膜基质细胞蜕膜化对生殖成功至关重要。蜕膜化过程包括
子宫内膜间质细胞的形态和功能变化。肌动蛋白-肌球蛋白细胞骨架
细胞形态的变化,并可能在细胞内蛋白质的穿梭中发挥作用,
蜕膜化蜕膜化是人子宫内膜间质细胞响应于
孕激素水平上升,并通过胚胎信号和孕激素维持整个妊娠期。
这个过程中的缺陷与子宫内膜异位症等疾病的生殖失败有关。
子宫内膜异位症的特征是在异位部位发现子宫内膜样组织,
伴有明显的盆腔疼痛、不孕和痛经,但其病理生理机制仍不清楚。的目的
建议是了解细胞骨架在蜕膜化过程中的功能作用,并确定
子宫内膜异位症妇女的基质细胞中这种异常是如何导致不孕的。的
已知Hippo靶同源物,雅普和TAZ,以及Notch 1信号传导介导免疫应答的起始。
蜕膜化反应,但在蜕膜化过程中调节这些途径仍然是未知的。先前
研究还表明,细胞骨架的显著变化与子宫内膜间质
细胞蜕膜化此外,细胞骨架动力学和Notch 1和雅普/TAZ信号转导在细胞凋亡中失调。
子宫内膜异位症我们假设细胞骨架介导了蜕膜化反应,并且在
患有子宫内膜异位症的不孕妇女为了检验我们在目标1中的总体假设,我们将研究直接肌动蛋白-肌球蛋白
子宫内膜异位症中Hippo/雅普/TAZ和NOTCH 1信号通路的细胞骨架调节
基质细胞蜕膜化,在目标2中,我们将确定改变的细胞骨架如何影响
子宫内膜异位症不孕妇女间质细胞的蜕膜化拟议的研究将涉及
细胞骨架调节调节基质细胞蜕膜化的关键分子机制。这些研究
将大大扩展申请人在细胞和分子生物学方面的技术专长。这些经验
与赞助商,共同赞助商和计划支持的专业发展相结合,将有助于
申请人发展所需的技能,以追求在基础科学研究的职业生涯。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Genna Moldovan', 18)}}的其他基金
Cytoskeletal regulation of the Hippo and Notch1 signaling pathways in endometrial stromal cell decidualization and endometriosis
子宫内膜基质细胞蜕膜化和子宫内膜异位症中 Hippo 和 Notch1 信号通路的细胞骨架调节
- 批准号:
10560477 - 财政年份:2022
- 资助金额:
$ 3.87万 - 项目类别:
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